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Cold Exposure & Other Mild Stressors for Increased Health & Longevity

Cold Exposure Exercise Fasting UCPs UCP1 UCP3 FGF21

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#101 Gordo

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Posted 04 March 2016 - 11:34 PM

Just some more thoughts about cold exposure, I don't feel like anyone has done the proper research yet to determine the effectiveness of various forms of cold exposure on BAT activation.  Many studies seem to just use cold rooms, some studies even had people sticking their legs on blocks of ice -- all of these methods might be "off base".  A proper comparative study could be hugely beneficial for science and humanity, so I hope someone runs one.  

 

The reason I'm thinking about this is because I see many reactions from people along the lines of "I couldn't do that, I hate being cold".  There's even a quote from this very thread "I don't like the idea of subjecting myself to cold, just because it's uncomfortable".  I have found that wearing a 58 degree (F) cooling vest that is very targeted to BAT and not cooling my whole body, is not in any way uncomfortable, in fact it is rather pleasant, and the more you become cold adapted, the more pleasant this becomes.  You can actually feel the BAT "kick in" and start generating heat.  Its funny because after a while in the cooing vest, its almost impossible to tell what the ambient temperature is.  Anyway, the image of a shivering guy in a freezing cold room trying to go about his daily routine probably isn't the best representation of this, but as far as I know, we really don't have data yet to say what cooling methods produce the best results.



#102 Dean Pomerleau

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Posted 05 March 2016 - 03:27 AM

Gordo,

I agree with your that more experimentation is needed with what cold exposure techniques are best for promoting and activating BAT in people. I too find cold not unpleasant once you get used to it. I think it is a mental thing for most people. My wife absolutely hates the cold, and is constantly complaining about it. I think it is a natural human reaction to something that has been potentially detrimental or dangerous during our evolutionary history.

It seems with some discipline and persistence, one can really train oneself to relish the cold, rather than shrink from it. I have a fan set up behind my stationary bike, blowing on my back as we speak. The temperature here in my basement is between 58 and 59 degrees. I've been leisurely peddling away for about 20 minutes, and I'm starting to feel what can best be described as a warm tingling sensation in the upper middle of my back, along my spine and in my trapezius muscles. I speculate that it might be the BAT kicking in. What is it that you are feeling when you get the sense that your BAT is kicking in? Anything like what I describe?

P.S. My Cool Fat Burner (original + 'Gut Buster' combo) arrived yesterday. It is amazingly heavy! It comes with 12 phases change cold packs, each of which weighs 625g, for a total of 7.5kg of cold packs, or 16.5 lbs. Much more than the 3kg listed on the coolfatburner.com website. I'm charging up the cold packs and will test it later today.

--Dean
There will never be peace in the world while there are animals in our bellies.

#103 Gordo

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Posted 05 March 2016 - 12:47 PM

Wow Dean, 7.5kg of PCM is more than 3 times what the techkewl came with, sounds great.  I'd like to see some pictures of everything.  Also what IS the phase change temp of those cooling packs?  I sort of had the impression that they were colder than the techkewl ones but I couldn't find that info on their site.

 

I'm not sure offhand if anyone has already mentioned this yet, but interestingly enough, BAT apparently even has a role in bone growth and bone density which may be of particular importance to anyone doing CR (but also important to everyone who lives long enough):

http://www.ncbi.nlm....pubmed/25388370

"Inducible brown fat is associated with higher bone mineral density, suggesting that brown fat interacts with bone growth in previously unrecognized ways." 

 

When BAT kicks in I have noticed a pleasant warming sensation mostly around my collarbones and ribs, after a cooling session and vest being removed for a little while, it is remarkable how hot those areas become.  Not sure of the best way to do it, but it would be interesting to compare skin temps at various locations say an hour after a cooling session.

 

This is probably going to vary by person, but I kind of feel like BAT around the ribs has been under-recognized by researchers.  BAT is more like muscle than fat, and anchors to bone.  The ribs at least in some people, seem to be covered with BAT, but not at the same density as the clavicle area.  The reason I think this is important is because the ribs are so close to the skin and have such big surface area compared to any other BAT "hot spots" (pardon the pun).  Remember that BAT can be "built up" but needs some foundation to start with, this makes the ribs of particular interest to me since they seem to have the most potential for "BAT growth".  I first noticed this in the cool fat burner guy's videos (but you can also see it in some before/after PET scan images from research studies, one pic included in this thread).  CFB guy's PET scan after BAT activation:

PET_Scan_Rib_BAT.png

 

Externally:

Rib_BAT_External.png

 

After a cooling session my own rib area (also clavicle area) are burning up like I imagine this guy's must be in the pic above.

 

FYI: I had a an entertaining (if somewhat surreal) experience last night wearing the cooling vest in bed while watching the movie "Everest" (where people are climbing in extreme cold and freezing to death, haha).  Good stuff, I highly recommend!


Edited by Gordo, 05 March 2016 - 12:55 PM.


#104 Saul

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Posted 05 March 2016 - 01:27 PM

My daily very cold showers leave me feeling cold -- but not shivering -- for several hours.

-- Saul

#105 Kenton

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Posted 05 March 2016 - 03:11 PM

Almost certainly not. I'm working on a big post on this very topic, but as a preview, it appears you actually have to be cold (i.e. have reduced core body temperature) to benefit. Turning the thermostat down and bundling up almost certainly defeats the purpose.

 

I am with Khurram about being too cold disrupting QOL (especially disrupting ability to think).  Like you, Khurram, I have a very low BMI -- and I reach "shiver level" rapidly and easily.  (By way of background, as Khurram knows first hand from visiting with me, I've surfed in the cold Pacific Ocean (So. Cal.) for the past dozen years while on CR--Consequently, I've familiarized myself with & tried to incorporate cold exposure into my daily routine even when not in the water.)  I've always tried to stay just shy of chill bumps / shivering; I check my temperature (daily) to make sure it's 96.3F or 97.2F (outside of eating windows).  OTOH, I am reconsidering and would probably go to greater cold exposure degrees (pun intended) if such greater amounts would combat my DNA from turning into alphabet soup.



#106 Dean Pomerleau

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Posted 05 March 2016 - 05:21 PM

A Tale of Three Rodents - Part 3: Bats

 

This is the third post in my three part series on long-lived rodents and BAT (brown adipose tissue) thermogenesis, in which I'll discuss bats. Note, in this post, lowercase 'bat' will always refer to the little flying creature, and uppercase 'BAT' will always refer to brown adipose tissue, if that weren't obvious.

 

But before discussing bats' BAT, I'll share a statistic I came across about BAT that is simply amazing, and will be quite relevant for bats. Review article [1] says the following:

 

BAT is characterised as possessing large amounts of the unique uncoupling protein (UCP) 1 which when activated enables the free-flow of protons across the inner mitochondrial membrane, resulting in the rapid dissipation of chemical energy as heat [ref]. Consequently, when maximally activated, BAT can generate up to 300 W[atts]/kg of tissue compared with 1 W[att]/kg from most other tissues [ref].

 

That 1 Watt/kg for other tissues seems on the low side - elite cyclists can generate a sustained 5-6 Watts/kg of body weight. Since their thighs are only a fraction (although a pretty large fraction) of elite cyclists' body weight, they are obviously generating a lot more than 5-6 Watts per kg of muscle fibers. But if you consider an elite cyclists body weight to be around 60kg, they are generating about 300 watts of total power (5W/kg * 60kg) that the pedals, using their entire body (e.g. cardiovascular system) to support it. It's quite astonishing how metabolically energetic BAT is. It doesn't take much to burn a lot of calories - comparable to rigorous exercise.

 

OK - back to bats. First, my bad. Bats aren't even remotely related to rodents. Sorry about that. From this page on Myths and Facts about Bats:

 

Bats are not flying mice; they are not even remotely related to rodents. Bats are such unique animals that scientists have placed them in a group all their own, called ‘Chiroptera’, which means hand-wing. Bats are grouped with primates and lemurs in a grand order called Archonta.

 

Several traits set bats apart from other mammals. No, it's not their sonar, which they share with other mammals like dolphins. Instead, bats are the only mammals to have achieved (self-)powered flight. Plus, and most relevant for our purposes, they live a very long time for their size. The little brown bat (LBB - Myotis lucifugus) is really quite tiny (see image below) - weighing in at only 5-14g. That is about 1/2 the size of naked mole rats, and 40-100x smaller than grey squirrels. But the LBB can live up to 30 years - rivaling even the naked mole rat for longevity. The (slightly) bigger big brown bat (BBB - Eptesicus fuscus, discussed below) weighs 15-20g, and doesn't live quite as long (~20 years max).

 

bat2.jpg Cute - isn't he!? :-)

 

LBBs eat 50% to 100% of their body weight in mosquitoes per night - which equates to about 5,000 and 10,000 mosquitoes! Their heart rate can vary from as low as 5-10 BPM during hibernation, to 200 BPM when at rest but not hibernating, to over 1000 BPM during flight. The LBB is an amazing creature!

 

But enough of the fascinating bat facts - the question is do long-lived bats have BAT?

 

Given how much energy they are burning simply at rest and in flight (with heart rates of 200 and 1000 BPM respectively), one might think they don't need to generate extra heat when not hibernating. And with a heart rate of on 5-10 BPM when hibernating, it would seem they can't be engaging in that much norepinephrine-induced BAT activity during that part of the year. But on the other hand, their small size and large surface area (including wings) means they radiate a lot of heat away, and they do hang out (literally) in cool, damp caves. So maybe they do require BAT to help them generate heat. 

 

So which is it? Lots of BAT, or not very much?

 

As you might have guessed by now, it appears that bats have lots of BAT!

 

I couldn't find data on LBBs specifically, but below is the table from [2], which measured the weight of various tissues & organs in Big Brown Bats (BBBs) both in summer, and during hibernation in winter:

 

ZQY3oPA.png

 

Let's compare these BAT numbers, both absolutely and in percentage terms, to rats. Below is a similar table from PMID 18593277 (discussed in this post), showing the amount of BAT in young (left column), old (middle column) and Old CRed (right column) rats. In absolute terms, the weight of BAT tissue in the BBBs and the rats is pretty similar, between 0.4g and 1g. So not all that remarkable. But then you realize that BBBs weighted ~25x less than the rats. The BAT in BBBs is between 2.8% (in summer) and 4.2% (in winter) of total body weight. That's huge! This compares with 0.1% to 0.15% of total body weight in rats. In other words, BBBs have ~30x more BAT than rats as a percentage of body weight.

 

WkUomfE.png

 

The authors of [2] suggest that the large amount of BAT the BBBs possess, especially in the winter, is critical for raising them from hibernation - basically the BAT enables them to jump-start their metabolism by burning calories stored in all that white adipose tissue to generate heat:

 

There remains little doubt that differences in time required for arousal are primarily a
consequence of seasonal differences in the mass of brown adipose tissue and therefore, in the
amounts of heat produced by this tissue. Both shunting of blood to anterior body regions
and initiation of the rewarming process depend largely on the ability of brown fat to assume
a comparatively high metabolic rate at low temperatures (Rauch 1973)...
 
Indeed, the success of [big brown bats] to elevate its body temperature in the cold depends
primarily on brown fat as a source of heat. Both nutritional blood flow studies (Rauch
1973; this study) and data from direct thermometry (Smalley and Dryer 1963; Hayward
et al. 1965; Rauch 1973; Studier 1974) suggest passive warming of organs of the posterior
body, and that shivering thermogenesis by skeletal muscle is not essential for the arousal
of this species (Hayward and Lyman 1967). 

 

But whatever the evolutionary reason, big brown bats (and almost certainly the little ones as well!), like grey squirrels and naked mole rats, have a LOT of BAT, and also like them, live a very long time relative to other small mammals.

 

Obviously this correlation between amount of BAT and extreme longevity in all three of these species does not necessarily imply causation. But when combined with all the other evidence outlined in this thread (which just reached 100 posts!) for the health & longevity benefits of increased BAT, it seems extremely suggestive to me...

 

--Dean

 

 

-----------

[1] Scientifica Volume 2013 (2013), Article ID 305763, 14 pages

 
Brown Adipose Tissue Growth and Development
 
Michael E. Symonds
 
Early Life Nutrition Research Unit, Academic Division of Child Health, School of Clinical Sciences, University Hospital, The University of Nottingham, Nottingham NG7 2UH, UK
 
Received 4 February 2013; Accepted 28 February 2013
 
Academic Editors: Y. Chagnon and G. Lopaschuk
 
 
Abstract
 
Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.
 
-------
[2] Écoscience Vol. 5, No. 1 (1998), pp. 8-17
 
Changes in body mass and fat reserves in prehibernating little brown bats (Myotis lucifugus)
Thomas H. KUNZ, John A. WRAZEN and Christopher D. BURNETT
 
 
Abstract
 
Changes in body mass, fat mass, lean dry mass, and energy content of little brown bats, Myotis lucifugus (LeConte), captured at a cave in southern Vermont, were quantified during the pre-hibernation period in late summer and autumn. Adults of both sexes showed maximum rates of increase in body mass from mid-August to mid-September, during which time the average gain was 2.3 g for males and 2.1 g for females. These gains represent 32.9% and 29.6% of the pre-hibernation body masses for adult males and females, respectively. Young-of-the-year of both sexes weighed about 1 to 2 g less than adults during most of the pre-hibernation period. In mid-September, adult females weighed significantly less than a cohort of adult females captured at a maternity roost on the same date. Adult bats reached their maximum pre-hibernating body mass in mid-September, whereas young bats reached their maximum pre-hibernating body mass one month later. From mid-July to mid-September, we found no significant differences in mean body mass between young males and females, but in mid-October when they entered hibernation, young females weighed significantly more than young males and almost as much as adult females. Young males and females arrived at the swarming-hibernation site in late summer with an average lean body mass and fat index approximately 20% lower than adults. By early October, young females achieved minimum adult levels of lean dry mass, but by the time they entered hibernation the lean mass of young males was still about 10% lower than adults. During the pre-hibernation period, lean dry mass and fat mass of all bats were significantly correlated with body mass. Regression equations derived from these data were used to estimate total energy content of bats. The acquisition of maximum fat reserves by M. lucifugus in the pre-hibernation period may be as important for successful reproduction as it is for sustaining hibernation. The fattest adult males may gain a reproductive advantage if they acquire enough energy reserves to sustain autumn mating and hibernation, and engage in multiple matings during the winter. The fattest females should gain a reproductive advantage by maximizing fat reserves before entering hibernation, and retaining sufficient energy reserves at the end of hibernation to facilitate ovulation. Relatively low survival and reduced fecundity in females at northern latitudes may reflect the relatively low fat reserves deposited by young females in their first autumn. 

There will never be peace in the world while there are animals in our bellies.

#107 Dean Pomerleau

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Posted 05 March 2016 - 07:09 PM

All,

 

Saul wrote:

My daily very cold showers leave me feeling cold -- but not shivering -- for several hours.

 

and Kenton wrote:

 Like you, Khurram, I have a very low BMI -- and I reach "shiver level" rapidly and easily... I've familiarized myself with & tried to incorporate cold exposure into my daily routine even when not in the water.  I've always tried to stay just shy of chill bumps / shivering; I check my temperature (daily) to make sure it's 96.3F or 97.2F (outside of eating windows). 

 

and Sirtuin wrote:

I do take cold showers regularly (primarily to escape the heat and to keep my skin moisturized) and leave a fan on, but it's difficult to avoid being fairly heat-acclimated and somewhat cold-sensitive in this environment.

 

I think there are three, closely-related but not identical, states being discussed related to cold, that could stand to be teased apart. The first is feeling cold - which is a subjective state. The second is being cold - i.e. having a low body temperature. The third is being in cold - i.e. being exposed to cold temperatures. 

 

I don't think it's possible to know definitively how these three are correlated with each other, or with BAT activity, in general or in CR folks in particular. But one thing is clear from my research - they aren't synonymous. For example, it's not unusual for CR folks to both be cold and feel cold, even when being in relatively warm ambient conditions that others find quite normal and tolerable. 

 

Here I'm going to go out on a limb, and say something people may not want to hear, but I predict being cold and feeling cold, especially when not being in cold ambient conditions, is an indication one has little BAT / BAT-activity, rather than being a positive sign of BAT synthesis or BAT activity.

 

From PMID 18593277 (discussed here), we know that old CRed rats have less BAT, as a percent of body weight, than old AL-fed rats. And as discussed in this post, PMID 23393181 found that anorexics (BMI 15.5), refed anorexics (BMI 18.8) had no detectable BAT, but were presumably both subjectively and literally colder than controls. In fact, it was only the "constitutionally lean" (CL) women (BMI 16.2) who were found to have BAT in abundance, along with a higher resting metabolic rate to support it:

 

 All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW (12%) subjects showed [measureable BAT activity].
 
Additionally, recall from this discussion that grey squirrels have a higher body temperature than other rodents, and don't appear to suffer from feeling cold (given how playful they are outdoors in winter) despite being in extremely cold conditions. And they have lot of BAT and BAT activity, on top of living a very long time for a rodent. 
 
All this suggest that being cold (low body temperature) or subjectively feeling cold aren't sufficient for, or even necessarily correlated with, elevated BAT amount or BAT activity. In fact, they may even be inversely correlated with elevated BAT.
 
Moreover, unless you are born with genes that promote BAT (like the 'constitutionally lean' women above), being in cold for several hours per day and eating enough calories to support it, is likely to be required in order to synthesize and activate BAT, especially in very lean, older people like most of us.
 
Surfing in the chilly ocean of northern California would certainly qualify as cold exposure, and will likely promote synthesis & activation of BAT, as long as one is eating enough calories... But simply "feeling cold, or actually being cold, for several hours after a cold shower" in presumably normal ambient conditions is suggestive to me that one lacks BAT and has trouble warming up as a result, rather than a sign that one is synthesizing or activating BAT.
 
--Dean

There will never be peace in the world while there are animals in our bellies.

#108 Saul

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Posted 06 March 2016 - 10:56 AM

Hi Dean, Kenton and Gordo!

My body temperature is always 96.(something) or 97.(something).

Kenton, I was very impressed by your BMI when you went to the front of the lecture room during a
talk at CR VIII --- the distance from your front to back looked like only 3-4 inches! (Perhaps an
illusion, but no doubt -- extremely impressive!)

I look forward (I hope) to your presence at CR IX!

:)

-- Saul

#109 Michael R

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Posted 06 March 2016 - 12:48 PM

Here I'm going to go out on a limb, and say something people may not want to hear, but I predict being cold and feeling cold, especially when not being in cold ambient conditions, is an indication one has little BAT / BAT-activity, rather than being a positive sign of BAT synthesis or BAT activity.
 
From PMID 18593277 (discussed here), we know that old CRed rats have less BAT, as a percent of body weight, than old AL-fed rats. And as discussed in this post, PMID 23393181 found that anorexics (BMI 15.5), refed anorexics (BMI 18.8) had no detectable BAT, but were presumably both subjectively and literally colder than controls. In fact, it was only the "constitutionally lean" (CL) women (BMI 16.2) who were found to have BAT in abundance, along with a higher resting metabolic rate to support it:
 

 All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW (12%) subjects showed [measureable BAT activity].

 
Additionally, recall from this discussion that grey squirrels have a higher body temperature than other rodents, and don't appear to suffer from feeling cold (given how playful they are outdoors in winter) despite being in extremely cold conditions. And they have lot of BAT and BAT activity, on top of living a very long time for a rodent.

Indeed. On the other hand, despite their depleting effects on BAT, we have extensive evidence that CR in rodents retards aging and extends maximum lifespan, and some limited evidence that human CR does the same (including the greater life expectancy of anorexics when concomitant substance abuse and hospitaized cases are excluded, despite the poor overall "lifestyle" of anorexics), whereas we have no interventional evidence that increasing BAT level or activity does either, or has any health benefits not attributable to obesity-avoidance. Indeed, the BMI-longevity evidence is a much bigger hurdle for the "BAT longevity" hypothesis than it is for CR, since nearly none of the lean people in the general population is doing anything remotely resembling CR, and a substantial proportion of them are constitutionally lean.



#110 drewab

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Posted 06 March 2016 - 01:54 PM

I hadn't heard the term constitutionally leanness until today.  I tried searching this site and Google for a definition, and I am wondering if it resembles something like this:

 

People who are underweight BMI (13 -17ish), but who don't have the usual problems that accompany that weight (ie. normal menstruation, normal thyroid, normal cardiac function, normal insulin sensitivity, etc.).  Is this accurate?



#111 Dean Pomerleau

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Posted 06 March 2016 - 02:31 PM

Drew,

 

I don't think there is an official definition for "constitutionally lean". As discussed in this post, the authors of PMID 23393181 defined it as follows: "constitutional leanness is a peculiar physiological condition whereby the body is resistant to fat storage, even in overfeeding conditions." 

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#112 Kenton

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Posted 06 March 2016 - 03:29 PM

...in the chilly ocean of northern California would certainly qualify as cold exposure ... 

 

My twin has strong CR biomarkers but only practices about 10% CR.  I wonder if it could be because he surfs in the same cold water.  As Saul noted, my BMI is fifteen and a half ish; my identical twin has a BMI of about twenty-five ish yet exhibits low WBC count, elevated TSH, (and FYI low HbA1c ), etc.  His biomarkers are roughly 80-90% as good as mine.  He eats well but restricts his calories only about 10 or 15%.


Edited by Kenton, 12 March 2016 - 02:58 PM.
Fix misplaced quote. I (Dean) don't have a BMI of 15.5ish!


#113 Dean Pomerleau

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Posted 06 March 2016 - 04:21 PM

Michael - wonderful! Finally a skeptic chimes in on the idea that BAT and BAT-activity promotes health/longevity.  This will be fun if you've got a few cycles to spare for these discussions (he says hopefully...).

 

You wrote:

On the other hand, despite [its] depleting effects on BAT, we have extensive evidence that CR in rodents retards aging and extends maximum lifespan,

 

Regarding CR's "depleting effects on BAT" as reported in PMID 18593277. In the quote you include, I point to the discussion of that study in this post. If you look at that discussion, you'll see that Valle et al did indeed see lower amounts of BAT in CRed rodents. But they also found the BAT the CR rodents did retain was much more active i.e. had a much higher expression of UPC1 as a result of mitochondrial biogenesis. The authors conclude (my emphasis):

 

In broad terms, we observed that old restricted animals compared to old ad libitum fed ones have a reduced BAT size, even normalized per body weight, which probably is due to a lower fat content and adipocyte number in the tissue. ... As happens in liver or skeletal muscle, CR was also shown to promote mitochondrial biogenesis in BAT. On the whole, this conservation of BAT thermogenic capacity may confer several advantages, such as a higher ability to respond to cold exposure or to control body weight when food supply is restored, and, therefore, be part of the rejuvenation mechanisms underlying the life-span extension induced by CR.

 

So in rodents at least (but apparently not people, at least according to the study of BAT in anorexics), CR spares some BAT, and the BAT that does remain appears to work extra hard to generate heat, in the scrawny, cold-sensitive rodents. So, far from discrediting the theory that BAT is beneficial and important for health / longevity, this study supports it, since BAT activity remains robust in CR rodents, and in fact could be argued to be a greater fraction of metabolic activity than in (well-insulated) controls.

 

But more fundamentally, when you say:

...we have extensive evidence that CR in rodents retards aging and extends maximum lifespan,

 

shouldn't you really say "we have extensive evidence that CR in rodents retards aging and extends maximum lifespan when rodents are exposed to cold conditions"?

 

As I pointed out in this post, and elaborated on in this one, PMID 9032756 yoked the weights of two groups of CR mice together so as to be identical, and kept one at thermal-neutrality (86°F) and the other at a "normal" (i.e. chilly-for-rodent) temperature of 72°F.  It was only the chilly CR mice that lived longer than controls. In fact, despite eating fewer calories than the chilly CR mice (and a heck of a lot less than AL-fed controls), the thermally-neutral CR mice didn't live any longer on average than AL-fed controls. This would seem to suggest cold exposure is a critical component of the "CR magic", despite requiring animals to eat more calories. Here again are the survival curves of the Control (CT/B6), Energy-Restricted, cool-housed (ER/B6) and Energy-Restricted, warm-housed (ERI/B6) mice:

 

Ni5cZ3p.png

 

So my question is - have there been other studies that contradict this result, i.e. that show CR extends lifespan in rodents even when housed at thermal-neutrality?

 

Next you wrote:

...whereas we have no interventional evidence that increasing BAT level or activity does either [retards aging or extends maximum lifespan], or has any health benefits not attributable to obesity-avoidance.

 

I realize it's huge, but have you read the earlier posts in this thread?

 

I'll divide my response into two sets - one for rodents and one for people.

 

Regarding your statement that there is no interventional evidence for BAT's benefits in rodents not attributable to obesity-avoidance:
  • Obviously PMID 9032756 just discussed flat-out contradicts your assertion, since CRed mice housed at what for them is an uncomfortably cool temperature ate 20% more, weighted the same, and lived 40% longer on average than equivalently-skinny CRed mice housed at a comfortably temperature. In this post, I discuss PMID 9032756 which found that housing C57BL/6 mice at "normal" (i.e. cool for them, ~68 °F) housing temperatures increases BAT expression by a factor of 22x compared with mice housed at thermal-neutrality. So between these studies, we see that cold exposure → ↑ BAT-activity → ↑ longevity even when both groups of rodents are CRed.
  • Cold exposure upregulates circulating fibroblast growth factor 21 (FGF21) in people by 37%, and FGF21 in mice BAT by a factor of 40x [1]. PMID 23066506 found that transgenic mice that overexpress FGF21 lived 40% longer than controls without the mutation, despite the FGF21-mutant mice eating a bit more than the normal mice. It's an argument in several steps (cold exposure → ↑ BAT → ↑ FGF21 → ↑ longevity), but it shows obesity-independent benefits of cold exposure & BAT.  See this post for more discussion. 
  • As discussed in this post, methionine restriction results in increased calorie intake per kg-BW, a 2 °F increase in body temperature, and a dramatic increase in UCP1 activity in BAT. As we know, methionine restriction results in multiple health benefits and  increases lifespan. Again several steps (MR → ↑ BAT activity → ↑ longevity), but suggestive of the role BAT plays in health & longevity, independent of its impact on obesity and despite it requiring consumption of more calories to support.
 
Regarding your statement that there is no interventional evidence for BAT's benefits in people not attributable to obesity-avoidance:
  • PMID: 24954193 (discussed here) found insulin sensitivity improved in parallel with BAT level in healthy male volunteers as a result of cold exposure, in a cross-over design where they served as their own controls.
  • While not interventional, in this post, I discuss PMID 26795284 which found in 4000 human subjects, "BAT activity negatively correlated with arterial inflammation (r=-0.178, p<0.01), a relationship that persisted after correcting for age and BMI (r=-0.147, p<0.01). ... high BAT was associated with a reduced risk of CVD events (P = 0.048) even after correcting for age (P = 0.037)."

 

Finally, you say:

...we have extensive evidence that CR in rodents retards aging and extends maximum lifespan,

 

Michael, you and I both know that the (sad) elephant in the room is that CR didn't extend lifespan in the species we care much more about, rhesus monkeys, beyond its effects on obesity avoidance. Perhaps it was because the monkeys were housed at thermal neutrality, as discussed here...

 

If CR works in cold-housed rodents but not in warm-housed rodents or warm-housed monkeys, doesn't that suggest something about what it might take for CR to work in people?

 

--Dean

 

--------

[1]   J Biol Chem. 2011 Apr 15;286(15):12983-90. doi: 10.1074/jbc.M110.215889. Epub

2011 Feb 13.
 
Thermogenic activation induces FGF21 expression and release in brown adipose
tissue.
 
Hondares E(1), Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya 
F.
 
Author information: 
(1)Department of Biochemistry and Molecular Biology and Institute of Biomedicine,
University of Barcelona, and CIBER Fisiopatología de la Obesidad y Nutrición,
08028 Barcelona, Catalonia, Spain. hondareselayne@ub.edu
 
 
FGF21 is a novel metabolic regulator involved in the control of glucose
homeostasis, insulin sensitivity, and ketogenesis. The liver has been considered 
the main site of production and release of FGF21 into the blood. Here, we show
that, after thermogenic activation, brown adipose tissue becomes a source of
systemic FGF21. This is due to a powerful cAMP-mediated pathway of regulation of 
FGF21 gene transcription. Norepinephrine, acting via β-adrenergic, cAMP-mediated,
mechanisms and subsequent activation of protein kinase A and p38 MAPK, induces
FGF21 gene transcription and also FGF21 release in brown adipocytes. ATF2 binding
to the FGF21 gene promoter mediates cAMP-dependent induction of FGF21 gene
transcription. FGF21 release by brown fat in vivo was assessed directly by
analyzing arteriovenous differences in FGF21 concentration across interscapular
brown fat, in combination with blood flow to brown adipose tissue and assessment 
of FGF21 half-life. This analysis demonstrates that exposure of rats to cold
induced a marked release of FGF21 by brown fat in vivo, in association with a
reduction in systemic FGF21 half-life. The present findings lead to the
recognition of a novel pathway of regulation the FGF21 gene and an endocrine role
of brown fat, as a source of FGF21 that may be especially relevant in conditions 
of activation of thermogenic activity.
 
PMCID: PMC3075644
PMID: 21317437

There will never be peace in the world while there are animals in our bellies.

#114 AlPater

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Posted 07 March 2016 - 05:26 PM

I could not find the below paper in PubMed, but it sure gave me the sense that messing with mouse thermoregulation is not a good model of the human condition.  We do not get torpor.
 
I too will chose comfort.
 
 
"BAT weight also increased in mice exposed to
extremely warm temperatures of 35 and 37.5 degrees C, environments
that are well above the limits of normothermy for mice and must
have certainly been stressful.'
 
 
Journal of Thermal Biology Volume 37, Issue 8, December 2012, Pages 654–685
Review
Thermal physiology of laboratory mice: Defining thermoneutrality
C.J. Gordon
 
Abstract
 
In terms of total number of publications, the laboratory mouse (Mus musculus) has emerged as the most popular test subject in biomedical research. Mice are used as models to study obesity, diabetes, CNS diseases and variety of other pathologies. Mice are classified as homeotherms and regulate their core temperature over a relatively wide range of ambient temperatures. However, researchers find that the thermoregulatory system of mice is easily affected by drugs, chemicals, and a variety of pathological conditions, effects that can be exacerbated by changes in ambient temperature. To this end, a thorough review of the thermal physiology of mice, including their sensitivity and regulatory limits to changes in ambient temperature is the primary focus of this review. Specifically, the zone of thermoneutrality for metabolic rate and how it corresponds to that for growth, reproduction, development, thermal comfort, and many other variables is covered. A key point of the review is to show that behavioral thermoregulation of mice is geared to minimize energy expenditure. Their zone of thermal comfort is essentially wedged between the thresholds to increase heat production and heat loss; however, this zone is above the recommended guidelines for animal vivariums. Future work is needed to better understand the behavioral and autonomic thermoregulatory responses of this most popular test species.
 
Highlights
 
Laboratory mice have become the predominant test species in most disciplines of biomedicine.
 
Mice are housed at temperatures that subject them to moderate cold stress.
 
Their temperature and metabolisms stability is susceptible to a variety of drugs and pathological conditions.
 
This review focuses on the thermoneutral zone of laboratory mice.
 
The impact of temperature on growth, reproduction, organ development, and behavior is explored in detail.
 
Keywords
 
Ambient temperature; Metabolic rate; Evaporative water loss; Core temperature; Telemetry; Selected temperature; Huddling; Brown adipose tissue; Thermal conductance; Growth; Reproduction; Fever; Aging
 
"4.6. Torpor
 
Mice andseveralotherspeciesofrodentswillundergotorpor
when deprivedoffoodorplacedonacaloricallyrestricteddiet
(Koizumi etal.,1992; Swoap andGutilla,2009; Solymar etal.,
2010). Torporimpliesastateofinactivityandreducedrespon-
siveness tostimuli.Duringtorpormicedisplayastateof heterothermy,
definedasthepatternoftemperatureregulationwhere
core temperaturevariation,eithernycthemerallyorseasonally
(e.g., hibernation),exceedsthelimitsofhomeothermy(IUPS
Thermal Commission,2001).Comparedtotheratwhichunder-
goes amildreductioninbodytemperaturewithcaloricrestriction
or deprivation(forreview, Gordon, 1990), thecoretemperatureof
mice deprivedoffoodcanplummet,stabilizingatafewdegrees
above theprevailingambienttemperatureandremainatthat
level forseveralhours.Toexemplifytorporinmice,thetime
course ofcoretemperaturealongwithheartrateandmetabolic
rate intelemeteredfemaleC57BL/6Jmiceatanambienttem-
perature of19 1C isshown(Fig. 16A andB).Onecansee
precipitous fallsincoretemperature,heartrate,andmetabolic
rate after 6 hoffooddeprivation.Metabolicrateandheartrate
are reducedbyatleast75%oftheirnormallevelsandremain
stablized duringthetorporresponse.Interestingly,themice
recover spontaneouslyafter 16 hinspiteofthecontinuation
of fooddeprivation(fordetails,see Swoap andGutilla,2009).
The fallincoretemperatureduringtorporwilldependonthe
prevailing ambienttemperatureandthermalcharacteristicsof
the cage(e.g.,bedding,nestingmaterial,airmovement,etc.).For
example, thereductioninbloodpressureandheartrateoffasted
mice maintainedatthermoneutralityisnotnearlyasmarkedas
when theyarefastedat23 1C (Williams etal.,2002). Core
temperature offooddeprivedmicemaintainedat28 1C falls
to 341 after thefirstdayoffasting,recovers,andthenfallagain
to 29 1C aftertheseconddayoffasting(Kanizsai etal.,2009).
Torpor isconsideredtobeaprotectiveresponseinmice,
allowing fortheconservationofenergyreservesduringtimesof
food restrictions.Clearly,thereductionsinrestingmetabolicrate
during torporimprovethechancesofsurvivinglongboutswhen
food isunavailable(see Fig. 16A). Thispatternappearstobe
typical forfood-deprivedmice.Theabilitytoenterandrecover
from torporpresentsaremarkablechallengetothemouse’s
thermoregulatoryandcardiovascularsystemwhichisjustbegin-
ning tobeunderstood(Swoap andGutilla,2009).
 
It iswellknownthatcaloricrestrictioncanleadtoamarked
improvement inlifespaninrodentsandothermammals
(Turturro etal.,1999; Speakman andMitchell,2011). Theanti-
aging effectsofcaloricrestrictionhavebeenattributedinpartto
the reductionsinbodytemperaturewhich,inturn,reduce
metabolism andgenerationofoxygenradicals.Inadditiontoits
use inanti-agingstudies,caloricrestrictionisalsousedto
maintain miceandotherrodentsatafixedweightsothatthey
will performinanoperanttaskparadigmusingfoodasreinforce-
ment. Koizumi etal.(1992) monitored coretemperatureby
telemetry inmaleandfemaleB6micethatwerecalorically
restricted withdailyallotmentsoffoodthatessentiallymain-
tained bodyweightat20gcomparedto 40 gincontrolanimals.
The 24hbodytemperatureofthecaloricallyrestrictedmicewas
reduced dramaticallybythistreatment(Fig. 17A). Forexample,
control micemaintaintheircoretemperaturebetween35–39 1C,
24 hperday,whereascaloricallyrestrictedmicemaintainedtheir
temperature inthis35–39 1C rangeforonly12h/dayandarange
of 23–27 1C for3–6h/day.Inastudyfromthesamelaboratory,
6 montholdmicethathadbeenrearedonadietthatwas 60%
of theadlibfedanimalshadabodyweightthatwas58%ofthead
lib group.Whenfedatthestartofdarkcycle,coretemperature
was similarbetweengroupsbutthenplummetedatthemidpoint
of thedarkphaseandrecoveredslowlyduringtheday(Fig. 17B).
It isinterestingtonotethatthistreatmentwasassociatedwith
significant prolongationinlifespanandmarkedsuppressionin
the mitoticindexofcellsintheintestine,indicatingareductionin
cell turnover.Interestingly,thetorpidresponsewasessentially
blocked whenmicewerehousedatathermoneutraltemperature
of 30 1C althoughthemitoticindexhadnotcompletelyrecovered
by thisthermoneutraltreatment(Koizumi etal.,1992).
 
4.6.1. Torpor-cautionwhenusingfastingmiceforcalorimeter
studies
 
An overnightfastisatypicalprotocolforthemeasurementof
the basalmetabolicrateinclinicalstudies;however,such
procedures shouldbeappliedwithcautioninstudiesofsmall
mammals thathaveevolvedatorpormechanismtosurvive
periods oflimitedornofood.Inviewofthetorporresponsewith
such briefperiodsoffooddeprivation,onemustquestionessen-
tially anystudywheremicearefastedforproceduressuch
as bloodcollection,determinationofmetabolicrate,etc.Ifa
significant reductionincoretemperatureandmetabolicrateis
observed in6hthenthereislikelyapatternofphysiolo-
gical responseleadinguptothisevent.Thedecreaseinbody
temperature willdependontheprevailingambientconditionsas
well asthemicroenvironmentofthecage(e.g.,housingcondi-
tions ofvivariumlistedin Table 2). Alltogether,anymeasurement
of aparameterdirectlylinkedtometabolismsuchasblood
glucose inafastedmouseshouldbedonewhiletakingthese
factors intoconsideration.Asdiscussedearlier,theclassicstudy
by Herrington (1940) utilized micethatwerefooddeprivedforup
to 12hbytheendofthemetabolicmeasurements.Whiletheir
metabolic dataappeartoreflecttypicalvaluesformice,one
should questionhowthemetabolicprofilemaybeinfluenced
by thedurationoffooddeprivation.Ifthemicearehandledand
manipulated duringthemetabolictests,metabolicrateandbody
temperature probablyremainatnormallevelsbutthishas
apparently notbeenevaluated."
 
"Whenthemouse’s
thermal environmentdeviatesaboveorbelowtheidealzoneof
thermal comfortandmetabolicthermoneutrality,thereisgreater
stress onotherorgansandregulatorysystemsnotdirectlylinked
to thermoregulation.Thecriticalquestionis,‘‘howdoesthe
thermoneutral zoneformetabolicheatproduction,coretempera-
ture, andzoneofthermalpreferencecorrespondwiththeoptimal
temperature zonesfororgangrowthanddevelopment?
 
7.1. Brown adipose tissue
 
Brown adiposetissue(BAT)wouldappeartobeanorganthat
has evolvedprimarilyasasourceofheatgenerationforthermo-
regulation inrodentsandotherspecies.BATisanessentialorgan
for nonshiveringthermogenesisinmice,rats,andmanyother
species. Heldmaier(1974)demonstratedtherelationship
between ambienttemperatureandweightofBATwithapattern
that isakintoathermoneutralzone(Fig. 27). Albinoand
genetically hairlessmicewereadaptedtoeachtemperaturefor
four weeks.Itisimportanttonotethatthemicewerehoused
individually onawirescreenfloorwithnobedding.Thus,itis
difficult tocomparethesedatatothatofmicehousedinatypical
environment ofavivarium.Eliminatinganybeddingfornest
building allowedtheauthortostudythesoleeffectsoftempera-
ture acclimationonBATdevelopment.TheweightofBAT
increased inanearlinearfashionastemperaturedecreasedbelow
30 1C. Interestingly,BATweightalsoincreasedinmiceexposedto
extremely warmtemperaturesof35and37.5 1C, environments
that arewellabovethelimitsofnormothermyformiceandmust
have certainlybeenstressful.Itwasnotedthathistologically,the
BAT inwarmadaptedmicedifferedmarkedlyfromcoldaccli-
mated mice.BATofcoldexposedmicewashighlydevelopedand
multilocular. BATofthewarmacclimatedmicewasunilocular,
looking morelikewhiteadiposetissue.ItisalsoclearthatBAT
hypertrophy isexacerbatedinhairlessmiceexposedtothecolder
temperatures butthereislittledifferenceinBATweightat
temperatures of21 1C andgreater.Morerecently, Zhao etal.
(2010) found aneardoublingintheweightofBATinmaleSwiss
mice housedindividuallywithsawdustshavingsastheirexpo-
sure temperaturewasreducedfrom23to15to8toO 1C intwo
week intervals.Thiswasassociatedwithsignificantelevationsin
serum T3 levels andreductionsin T4."
 
"11.1. Conclusion: Mice are unique thermoregulators
 
Thermal physiologists strive to study the many facets of
thermoregulation of species with a rich variety of morphological
adaptations. Volumes have been written about animals with
unique thermoregulatory characteristics, such as arctic and tropical
mammals that have remarkable tolerances to extremely
high or low ambient or body temperatures. Likewise, evolution,
natural history, and selective breeding are all attributes that make
the mouse a unique thermoregulator. Researchers that use mice
as a human surrogate are certainly aware of the many caveats
that limit extrapolation from mouse to human. Mice are not
miniaturized versions of rats or humans in terms of their
thermoregulatory system despite the fact that their average core
temperatures differ by just 1 1C. We should consider the mouse as
a unique thermoregulator with its small size, narrow thermoneutral
zone, preference for comparatively warm ambient temperatures,
and ability to allow core temperature to vary widely
in some environments or regulate in others. This is especially true
in the use of mice and other rodents to study human metabolic
syndrome, as discussed in recent excellent reviews by Overton
(2010) and Cannon and Nedergaard ( 2011). In view of the recent
growth in the use of mice as test organism for most biomedical
disciplines, we need to have a better understanding of their
thermoregulatory characteristics."

Edited by AlPater, 07 March 2016 - 05:31 PM.


#115 Dean Pomerleau

Dean Pomerleau
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Posted 07 March 2016 - 05:54 PM

Thanks Al.

 

You quoted from the paper that warm temperatures increased BAT too:

 

"BAT weight also increased in mice exposed to
extremely warm temperatures of 35 and 37.5 degrees C, environments
that are well above the limits of normothermy for mice and must
have certainly been stressful."
 
What you left out was the next sentence, which showed the warm-induced BAT looked more like regular (white) fat and quite different from cold-induced BAT:
 
It was noted that histologically, the
BAT in warm adapted mice differed markedly from cold acclimated
mice. BAT of cold exposed mice was highly developed and
multilocular. BAT of the warm acclimated mice was unilocular,
looking more like white adipose tissue.
 

So it doesn't look like warm-exposure results in the same kind of BAT as cold-exposure after all.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#116 Dean Pomerleau

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Posted 08 March 2016 - 05:53 PM

For any non-wimps out there who are willing to entertain the idea of cold exposure, a couple new studies out this week may be of interest.

 

First off, [1] measured BAT and BAT-activity in men who were either Young & Lean (age ~25m, BMI ~22), Young & Obese (age ~25, BMI ~32), or Old & Lean (avg age ~54, BMI ~23).

 

They found the old-lean subjects (like us!) had less BAT-activity (left) and BAT-volume (right) than young-lean or young-obese. Here are the graphs:

 

H0vsZxT.png

 

Notice in particular the entire old-lean group had virtually zero BAT volume (right graph). Visually, you can see the BAT volume for typical members of the three groups is pretty strikingly different:

 

v8kx5GP.png''

 

The Young Obese (right) had less BAT than the Young Lean (middle), but the real dramatic difference is between the Old Lean (left) and the other two groups.  And the skinniest dude in the Old Lean group had a BMI of 21.7!

 

Given how much leaner most serious CRers are than any of the men in the Old Lean group in this study, and given that most CRers report having trouble with thermoregulation (i.e. feeling cold and having low body temperature), it seems likely most of us have virtually no BAT, unless we take steps to actively promote it...

 

Fortunately, the second study out this week [2] might suggest an answer for how to do just that. It found the combination of mild cold exposure & capsaicin worked synergistically to promote the conversion of white adipose tissue (WAT) into BAT-like 'beige' adipose tissue in mice.

 

First, on the issue of 'brown' vs. 'beige' adipose tissue, this paper observes that 'beige' adipose tissue in people appears to be the human-equivalent of 'brown' adipose tissue in rodents:

 

Rodents and humans possess two distinct forms of UCP1-positive thermogenic
adipocytes: classical brown adipocytes and beige adipocytes (also referred to as brite
adipocytes). While classical brown adipocytes and beige adipocytes share many functional
characteristics (i.e., thermogenesis), they are distinct cell types at developmental, anatomical,
and molecular levels. Classical brown adipocytes are prenatally derived from a subset of
dermomyotom, whereas beige/brite adipocytes postnatally emerge within white adipose tissue
(WAT) in response to a certain environmental cues, such as chronic cold exposure, exercise,...
 
Of note, it has been shown that molecular signatures of adult human BAT resemble mouse beige
adipocytes (12, 14-17)... Furthermore, chronic cold exposure up to 6 weeks was able to recruit
new active BAT depots in adult humans who did not possess appreciable levels of BAT depots
before cold exposure (18-20). Importantly, an emergence of the newly recruited BAT was
associated with an increase in cold-stimulated energy expenditure or with improved post-
prandial insulin sensitivity. These studies suggest that adult human BAT is largely composed of
the recruitable form of thermogenic adipocytes, that is, beige adipocytes. Hence, understanding
molecular circuits that preferentially promote beige adipocyte biogenesis may provide a new
opportunity of anti-obesity therapies for obese or old subjects who do not possess active BAT
depots. 

 

So that's interesting. 

 

But onto what the study found. They fed mice a high fat diet, and divided them into three housing temperature groups (cool-housed 17°C, regular temperature (RT)-housed 23°C, or neutral-temperature-housed 30°C) and two capsaicin groups, depending on whether they got capsaicin (CSNs+) or not (CSNs-). So that makes six different groups. Here are the body weights of the six groups over time. 

 

dO7BVZG.png

 

First off - notice at the thermoneutral housing temperature of 30°C (right graph), capsaicin did not impact body weight. In fact the capsaicin group weight slightly more by the end of the study than the control (CSN-) group. They ignore this thermal neutral 30 °C group throughout the rest of the analysis, which is unfortunate. But this alone suggests that capsaicin only boosts BAT when coupled with cold exposure. 

 

Perhaps the most interesting thing is that the combination of cold exposure and capsaicin (CE+Cap) had a bigger impact than the sum of the two treatments when applied individually - i.e. the two treatments were synergistic. That can be seen in the graph above on the left, and is called out in the paper as follows:

 

Strikingly, the anti-obesity effect by capsinoids was significantly enhanced under mild cold at
17°C (Fig. 1A). This anti-obesity effect by the combination of capsinoids and mild cold
exposure was synergistic because capsinoids supplementation under 17°C led to a 31%
suppression of diet-induced body weight gain compared to control mice, whereas capsinoids or
mild cold exposure alone reduced body weight gain by 14% and 12%, respectively. The synergy
is statistically significant based on the analysis by interaction plot (P=0.03). This synergistic anti-
obesity effect was independent of changes in energy intake and behavior because no major
difference was observed in food intake and locomotor activity between vehicle and capsinoids
treated groups both at ambient and cold temperature (Fig. S1A and B).

 

Check out the highlighted text at the bottom. The CE+Cap group gained 31% less weight, without a significant difference in food intake or physical activity.

 

And it wasn't just weight that CE+Cap dramatically and synergistically impacted. Here is a graph of fasting glucose (left), fasting insulin (middle) and BAT-thermogenesis-induced oxygen consumption (right). As you can see, the CE+Cap group (i.e. CSNs+ @ 17 °C) had a lot lower fasting glucose and insulin, and a lot more oxygen consumption resulting from BAT stimulation.

 

kzCfRJC.png

 

The authors of [2] go on to suggest that cold exposure and capsaicin may increase BAT development via two distinct, rather complicated neural pathways, illustrated here:

 

DVKEAP3.png

 

 

Interestingly, study [3] found that in people, six weeks of mild cold exposure (17 °C for 2h/d) or six weeks of capsaicin supplementation (9mg capsinoids / day), tested independently, both resulted in about a 200kcal/day boost in cold-induced thermogenesis (CIT), as can be seen in the graphs below:

 

4lnsdHY.png

 

Note what [3] found was not that capsaicin increased energy expenditure in general. Capsaicin increased energy expenditure in response to cold exposure (i.e. cold-induced thermogenesis, or CIT). So here again, it was cold exposure plus capsaicin that had the effect. 

If [2] translates from mice to people, than the combination of chronic cold exposure and capsaicin may even be enough to boost BAT in us skinny old CRers.

 

Recall, as Michael pointed out in this post, this study [4] found daily chilli pepper consumption was associated with a 14% reduction in all-cause mortality.

 

I already eat a modest amount of chilli powder and fresh chilli peppers, but I've gone ahead and ordered this capsaicin supplement to really test the idea of combining cold exposure and capsaicin.

 

--Dean 

 

------------

[1] J Nucl Med. 2016 Mar;57(3):372-7. doi: 10.2967/jnumed.115.165829. Epub 2015 Nov

25.
 
Differences in Sympathetic Nervous Stimulation of Brown Adipose Tissue Between
the Young and Old, and the Lean and Obese.
 
Bahler L(1), Verberne HJ(2), Admiraal WM(3), Stok WJ(4), Soeters MR(5), Hoekstra 
JB(3), Holleman F(3).
 
 
Brown adipose tissue (BAT) could facilitate weight loss by increasing energy
expenditure. Cold is a potent stimulator of BAT, activating BAT primarily through
the sympathetic nervous system (SNS). Older or overweight individuals have less
metabolic BAT activity than the lean and young, but the role of the SNS in this
decline is unknown. We aimed to determine whether this lower metabolic BAT
activity in older or overweight individuals can be explained by a lower SNS
response to cold.METHODS: This was a prospective observational study. We included
10 young obese, 11 old lean, and 14 young lean healthy men. All subjects
underwent (18)F-FDG PET/CT and (123)I-meta-iodobenzylguanidine ((123)I-mIBG)
SPECT/CT after an overnight fast and 2 h of cold exposure. Metabolic BAT activity
was expressed as volume and as SUVmax of (18)F-FDG. BAT SNS activity was
expressed as volume and as the ratio between (123)I-mIBG uptake in BAT and a
reference region (SQUVmax of (123)I-mIBG).
RESULTS: SUVmax, BAT volume, and SQUVmax were significantly different between
young and old (SUVmax, 7.9 [range, 4.2-17.3] vs. 2.9 [range, 0.0-4.0]; volume,
124.8 [range, 10.9-338.8] vs. 3.4 [range, 0.0-10.9]; and SQUVmax, 2.7 [range,
1.9-4.7] vs. 0.0 [range, 0.0-2.2], respectively) (all P < 0.01) but not between
lean and obese (SUVmax, 7.9 [range, 4.2-17.3] vs. 4.0 [range, 0.0-13.5] [P =
0.69]; volume, 124.8 [range, 10.9-338.8] vs. 11.8 [range, 0.0-190.2] [P = 0.64]; 
and SQUVmax, 2.7 [range, 1.9-4.7] vs. 1.7 [range, 0-3.5] [P = 0.69],
respectively). We found a strong positive correlation between BAT activity
measured with (18)F-FDG and (123)I-mIBG in the whole group of BAT-positive
subjects (ρ = 0.82, P < 0.01).
CONCLUSION: Both sympathetic drive and BAT activity are lower in older but not in
obese men.
 
PMID: 26609175

 

---------

[2] Diabetes. 2016 Mar 2. pii: db150662. [Epub ahead of print]

 
A synergistic anti-obesity effect by a combination of capsinoids and cold
temperature through promoting beige adipocyte biogenesis.
 
Ohyama K(1), Nogusa Y(2), Shinoda K(3), Suzuki K(2), Bannai M(4), Kajimura S(5).
 
 
Beige adipocytes emerge postnatally within the white adipose tissue (WAT) in
response to certain environmental cues, such as chronic cold exposure. Because of
its highly recruitable nature and relevance to adult humans, beige adipocytes
have gained much attention as an attractive cellular target for anti-obesity
therapy. However, molecular circuits that preferentially promote beige adipocyte 
biogenesis remain poorly understood. Here, we report that a combination of mild
cold exposure at 17°C and capsinoids, a non-pungent analog of capsaicin,
synergistically and preferentially promotes beige adipocyte biogenesis and
ameliorate diet-induced obesity. Gain- and loss-of-function studies show that the
combination of capsinoids and cold exposure synergistically promotes beige
adipocyte development through the β2-adrenoceptor signaling pathway. This
synergistic effect on beige adipocyte biogenesis occurs through an increased
half-life of PRDM16, a dominant transcriptional regulator of brown/beige
adipocyte development. Our observations document a previously unappreciated
molecular circuit that controls beige adipocyte biogenesis and suggest a
plausible approach to increase whole body energy expenditure by combining dietary
components and environmental cues.
 
PMID: 26936964
 
------------
[3] J Clin Invest. 2013 Aug;123(8):3404-8. doi: 10.1172/JCI67803. Epub 2013 Jul 15.
 
Recruited brown adipose tissue as an antiobesity agent in humans.
 
Yoneshiro T(1), Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T,
Saito M.
 
Author information: 
(1)Department of Anatomy, Hokkaido University Graduate School of Medicine,
Sapporo, Japan. yoneshiro@med.hokudai.ac.jp
 
 
Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to 
cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron
emission tomography and computed tomography, we previously reported that BAT
decreases with age and thereby accelerates age-related accumulation of body fat
in humans. Thus, the recruitment of BAT may be effective for body fat reduction. 
In this study, we examined the effects of repeated stimulation by cold and
capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT 
activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure
(EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity
independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 
weeks resulted in a parallel increase in BAT activity and CIT and a concomitant
decrease in body fat mass. Changes in BAT activity and body fat mass were
negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks
increased CIT. These results demonstrate that human BAT can be recruited even in 
individuals with decreased BAT activity, thereby contributing to body fat
reduction.
 
PMCID: PMC3726164
PMID: 23867622
 
---------
[4] BMJ. 2015 Aug 4;351:h3942. doi: 10.1136/bmj.h3942. 
 
Lv J, Qi L, Yu C, Yang L, Guo Y, Chen Y, Bian Z, Sun D, Du J, Ge P, Tang Z, Hou W, Li Y, Chen J, Chen Z, Li L;
China Kadoorie Biobank Collaborative Group. 
 
 
PubMed PMID: 26242395;
PubMed Central PMCID: PMC4525189.

There will never be peace in the world while there are animals in our bellies.

#117 Dean Pomerleau

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Posted 10 March 2016 - 12:47 PM

All,

 

In this post I discussed study [1], which found that cold exposure not only increases BAT in mice so they can burn more calories to stay warm, but it also shifts their gut microbiome and microvilli of their intestine in a way that makes them more efficient at extracting calories from food to support the extra calories required for thermogenesis. Surprisingly, doing a "microbiota transplant" (i.e. poop transplant) from cold adapted mice to warm-housed mice caused them to develop more brown/beige adipose tissue, increase their thermogenesis, improved their insulin sensitivity, and increased their gut's calorie extracting efficiency too.

 

Al Paper pointed me to a new commentary [2] in the New England Journal of Medicine about the significance of [1]. It has a few interesting (and potentially relevant for us) details I'd overlooked. First off, here is the graphical abstract of [1] that is included in [2], showing in pictures the results I described in words above:

 

VG8ueC9.png

 

Here is a quote about the main results of [1]:

 

 This new work shows that prolonged cold exposure induces a massive increase in the
absorptive surface of the gut, in association with reduced apoptosis of the cells making up its
microvilli. Once again, this effect could be achieved simply by transplanting cold-adapted
gut microbiota to germ-free hosts. 

 

What I hadn't noticed when I read [1] originally were the details of the gut bacteria changes that happened as a result of cold exposure, described as following in [2]:

 

Which specific components of the microbiota mediate this effect? The authors show that cold
causes a profound increase in the ratio of Firmicutes to Bacteroidetes, as well as almost a 
complete loss of Verrucomicrobia species, including Akkermansia muciniphila; such changes have
been noted previously in mouse models of obesity and are associated with increased energy
extraction from food.3 When A. muciniphila was added back to the cold-adapted flora, the
effect of cold on increased gut absorption was blocked.

 

Why is this result particularly noteworthy? Because there are species of gut bacteria that uBiome.com measures - so (and several of us) have personal data on this over time and in comparison with others. In particular, I had a uBiome test done in November of 2013, and then two (a couple weeks apart) in late October and early November of last year - which nicely controls for seasonal variations. 

 

As I discussed in this post, I appear to have 2x more Firmicutes relative to Bacteroidetes in my latest tests, and be enriched in Firmicutes relative to the general population. Between 2013 and 2015, my firmicutes went up from 62% of my total bacteria to a two-test average of 74% of my total bacteria. Regarding the other type of bacteria explicitly mentioned, the Verrucomicrobia species, and in particular Akkermansia muciniphila - in 2013 Verrucomicrobia accounted for 1.11% of my bacteria, which was about half the 2.07% of the typical person in uBiome's database. As of 2015, my Verrucomicrobia level had dropped to a two-test average of 0.38%, which is only about 1/5th the level a typical person. 

 

Both of these shifts (i.e. an ↑ in Firmicutes and ↓ in Verrucomicrobia) are in the same direction as the cold-exposed mice. Interestingly, as of the date of those two 2015 tests, I wasn't yet intentionally engaged in my cold exposure experiments. It will be interesting to see if/when I get my next round of uBiome tests whether I've shifted even further in the direction of the cold-adapted gut microbiome.

 

Regarding calorie extraction efficiency as a result of cold exposure. Over the last several months that I've been doing intentional cold exposure, I've gained three pounds (115 → 118 lbs, BMI 17.2 → 17.7), despite not obviously or intentionally eating more calories. But I I don't weigh and track all my food these days, so I can't rule out extra calories as the cause of the modest weight gain.

 

Does anyone else, cold-adapted or not, have uBiome data on Firmicutes and Verrucomicrobia they'd be willing to share? Zeta, I know you've had a uBiome test. Care to share (if you're feeling better, I hope)?

 

--Dean

 

 

-------------
[1] Cell. 2015 Dec 3;163(6):1360-74. doi: 10.1016/j.cell.2015.11.004.
 
Gut Microbiota Orchestrates Energy Homeostasis during Cold.
 
Chevalier C, Stojanovic O, Colin DJ, Suarez-Zamorano N, Tarallo V, Veyrat-Durebex C, Rigo D, Fabbiano S, Stevanovic A, Hagemann S, Montet X, Seimbille Y, Zamboni N, Hapfelmeier S, Trajkovski M.
 
 
Highlights
 
Cold exposure leads to marked changes in the gut microbiota composition
 
Cold microbiota transplantation increases insulin sensitivity and WAT browning
 
Cold exposure or cold transplantation increase the gut size and absorptive capacity
 
Reconstitution of cold-suppressed A. muciniphila reverts the increased caloric uptake
 
Abstract
 
Microbial functions in the host physiology are a result of the microbiota-host co-evolution. We show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold, however, the body weight loss is attenuated, caused by adaptive mechanisms maximizing caloric uptake and increasing intestinal, villi, and microvilli lengths. This increased absorptive surface is transferable with the cold microbiota, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis-the effect diminished by co-transplanting the most cold-downregulated strain Akkermansia muciniphila during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand.
 
PMID: 26638070
 
-------------
[2] N Engl J Med 2016; 374:885-887 March 3, 2016 DOI: 10.1056/NEJMcibr1515457
 
Burning Fat by Bugging the System
 
Evan D. Rosen, M.D., Ph.D.
 

There will never be peace in the world while there are animals in our bellies.

#118 Dean Pomerleau

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Posted 10 March 2016 - 04:49 PM

Cool Fat Burner Review

 

All,

 

I've had my Cool Fat Burner (CFB) system for about a week and have been using it consistently so I figured it was time to do a review. First, I want to give a shout out to Eric, the person behind the CFB. From all the great videos of experiments he's done on himself, he's definitely a man after my own heart! Plus, after I ordered my CFB, I emailed him a link to this thread, and he was kind enough to send me a 4-pack set of soft cool packs, to add to the 12 solid "hybrid hardcore" packs I ordered with the Combo System I purchased ( $158, but $185 w/ tax & shipping) . Each of them weights about 625g, so all 16 add up to 10kg, or 22lbs of cooling packs. That's a lot of cool!

 

The first thing I did was an experiment to compare the two different types of cooling packs with a regular ice pack from my freezer, and with a block of ice, in terms of how long it took them to warm up. Here is a picture of the setup, with all four cold packs on a table in my 60 °F basement:

 

3FQmN4z.png

 

 

The block of ice is on the lower right (frozen in a plastic container), the regular cold pack is in the upper left (labelled 'Ultra'). The solid "hybrid hardcore" CFB pack is the white one on the lower left, and the flexible "soft" CFB pack is the blue one in the upper right. The orange thing is the non-contact thermometer I used to measure temperature (at the middle spot of each pack) every 20 minutes during the experiment, as measured by the timer shown in the lower right.

 

Here is a graph of the temperatures of the three packs and the block of ice during the six hours after I took them out of the freezer:

 

e7ONTOE.png

 

As you can see, at the time of the first 20 minute reading, the two CFB packs were significantly colder than regular cold pack and the block of ice. I was very surprised by this, so I measured all four of them multiple times and the difference persisted. In fact, for almost 4 hours the two CFB packs remained colder than either the block of ice or the regular cold pack. You'll also notice that at around 1.5 hours, the CFB soft pack (purple line) started warming up somewhat faster than the solid pack (blue line). Keep in mind though these were sitting out on a table in a cold room, so they stayed colder longer than they would if pressed against a warm human body.

 

Overall, I was very impressed with how well the CFB packs kept their cool. In fact, I may even consider using them to keep my food cold next time I travel! The solid "hybrid hardcore" packs stay cold longer than the flexible pack, but the flexible packs have the advantage of conforming to your body right away (see below). So it might be worthwhile to get some of each.

 

Now the review of the CFB system itself. As I indicated above, I bought the Combo Package, which included the original "Cool Fat Burner" (CFB) and the "Cool Gut Buster" (CGB). Here is the picture of the two from the CFB website:

 

combo-25-per-off-265x240.jpg

 

 

I bought both in size "medium" which seems a perfect fit for my 5'9", slim frame. As you can see from the picture, the CFB wraps over your shoulders, putting 4 cold-packs on your upper chest, neck and upper back area, where much of the brown adipose tissue in people is located. The CGB has straps that go over the shoulders and hangs down around your abdomen, below the level covered by the CFB. Together they cover my entire torse completely, as shown in the pictures below. The medium size CGB has pockets for 6 cold-packs. So when I'm wearing the CFB and CGB together (as shown below), that's a total of 10 packs, or almost 14 lbs of ice packs. It's really quite intense, even for me, whose been engaged in cold exposure for a while now. Here are a few pictures of me in full regalia:

 

Ucd0DSM.png  HgbYhUp.png  vIYSRWv.png

 

The third photo, with hat and gloves, is how I typically dress while using the CFB/CGB, to keep my head and hands warm as Eric recommends. The white patches you see around my neck area and towards the bottom in the middle image is frost on the outside of the vests from the cold packs underneath. As I said, it's pretty intense... As you can see, I'm wearing a t-shirt between the CFB/CGB and my skin. I haven't yet got up the courage to try wearing them without a shirt, like Eric does. That would really be intense.

 

Other than the intense cold (which I find exhilarating!), the CFB and CGB are quite comfortable to wear. They can be made quite loose or quite snug, depending on how you adjust the velcro straps, and this can be used to adjust the intensity of the cooling experience.

 

Regarding which packs to use for which pockets. I've found the six pockets of the CGB can be filled with the solid packs, since at least on me, they hang pretty straight down, i.e. don't have to conform to a curved belly. For the four pockets of the CFB, I've found putting the soft, flexible packs in the two pockets on the back works best. That way they conform to the two bones that stick out in the upper back, and allow me to comfortably lean back against the seat of my stationary bike right away, which I pedal leisurely to keep from getting too cold while wearing the CFB/CGB. I find putting two of the solid packs in the front pockets of the CFB works well, especially if I freeze them with a slight curve so they conform to my chest.

 

Regarding how long the packs stay cold when in use. I've been wearing the gear now for about 2 hours while composing this message and doing other stuff on the computer. The cold is still intense. Looking down, I still see the frost on the outside of the CFB on my chest as shown in the images above. So the cold lasts for a long time, at least in my basement man-cave, which is 62°F this afternoon.

 

How's it feel? Cold! In shorts and a t-shirt, but with the hat and gloves on, and with leisurely pedalling on my stationary bike, I can keep from shivering. But I've got a serious case of the goosebumps and the hairs on my arms and legs are really standing on end! 

 

Overall, I highly recommend the CFB/CGB for anyone who wants to experiment with cold exposure. If you want to save money and can do without the highest intensity cooling experience, you could go with just the CFB, rather than both the CFB/CGB combination. But I think you'll definitely want to get an extra set of 4 cold packs on top of the 4 that come with it. I'd probably recommend a set of 4 solid ones and a set of 4 soft ones. That way you can have two of each type in the CFB while the other two sets of two are charging in the freezer for uninterrupted cooling!

 

In short, if anything can promote and activate BAT in older, thin people like us, it will be the CFB/CGB. But if you are new to cold exposure, I definitely recommend taking it slow, working your way up to sending several hours wearing the gear, and keeping your hands, feet and head warm.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#119 Gordo

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Posted 11 March 2016 - 01:07 PM

Thanks for the great review plus the other study info.  The CFB is FAR colder (and heavier) than the cooling vest I've been using.  I'm tempted to buy one for comparison purposes, but am also thinking it might be over the top and if I wanted that much cold why not just use some standard blue liquid gel cooling packs. The vest I have produces a very comfortable temp even against bare skin, and is very light weight -- probably more "palatable" for an average person although you'll probably get more BAT growth with the more extreme vest.  Would REALLY love to see some actual data on that though.

 

Regarding the study with capsaicin, observing a synergistic effect with cold exposure...  The study mentioned supplementation with 9mg capsinoids / day.  Any idea what that translates into as far as either common supplement forms or hot pepper form?  Note this one seems like a good deal, 250 caps, 500mg of 40,000 heat unit pepper.  The review comments are hilarious, I also noted some comments about the glucose lowering effect.  

 

I have also upped my hot pepper consumption, but may do even more now.

 


Edited by Gordo, 11 March 2016 - 01:20 PM.


#120 Dean Pomerleau

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Posted 11 March 2016 - 04:49 PM

Gordo,

 

I agree. The CFB is pretty hardcore. A lot less stylish and "user friendly" than the TechKewl vest you bought, but probably also more likely to stimulate BAT synthesis and activation. Today was my weekly venture from my neighborhood to grocery shop at Aldi's and to stock up on durian at the Asian Market. It was still cool outside (~50 °F) and I had the windows open in the car, but I also decided to wear the CFB for extra cooling in the car. It worked well. But I took it off before going in the store(s). In contrast, It looks like you could easily wear the TechKewl vest around town, especially if you wear a shirt over it. 

 

Regarding the potency of the capsaicin capsules necessary to promote BAT activation. The Nature's Way "Cayenne 40,000 H.U." supplements I ordered came today. Haven't tried them yet - I'm waiting until I eat tomorrow morning. On the bottle it says "450mg cayenne pepper" per capsule, and in the text it says "guaranteed 0.25% capsaicin". So each capsule would have a little over 1 mg of capsaicin. Recall in study [1], the researchers gave subject 9mg of capsinoids/day. The capsinoids are a proprietary blend derived from a special cultivar of sweet peppers (CH-19 variety), that aren't very pungent, but that supposedly have a lot of capsaicin-like compounds that activate the sympathetic nervous system in the same way / degree as capsaicin, without the 'burn'. From the full text of [2] by the same authors as [1] (and the developers of this special capsinoid-rich CH-19 pepper, sold in capsule form in the US only by one company and not direct to consumer, but only through "healthcare professionals" - i.e. potential conflict of interest...) :

 

Capsinoids (capsiate, dihydrocapsiate, and nordihydrocapsiate) are capsaicin-like compounds found in a nonpungent type of red pepper, “CH-19 Sweet” (8, 9). Although capsinoids are much less pungent than capsaicin, they are as potent as capsaicin at increasing sympathetic nerve activity, thermogenesis, EE, and fat oxidation and in reducing body fat both in small rodents and humans (10–16).

 

So if the CH-19 sweet capsinoids are as potent as capsaicin as indicated, it would take around 8 of the capsaicin capsules per day to equal the three capsules of CH-19 Sweet capsinoids used in [1] and [2]. It's not clear how much the CH-19 Sweet capsules cost. According to this 2007 press release from the company:

 

The company says it is positioning the product for consumers who are truly dedicated to losing weight, and as such willing to spend more for Capsiate Natura. While Naulty [company president] said the pricing will be determined by individual health professionals, the daily dosage of three gelcaps should cost between $5 and $10 per day. 

 

Forgive me, but that's just ludicrous. The 180 capsaicin capsules I bought cost $10. So the 8 capsules / day required to get 9mg of capsaicin would cost less than $0.45 per day. Don't worry, I'm not going to try to get to that level. I'm going to start with one capsaicin capsule per day.

 

--Dean

 

--------

J Clin Invest. 2013 Aug;123(8):3404-8. doi: 10.1172/JCI67803. Epub 2013 Jul 15.
 
Recruited brown adipose tissue as an antiobesity agent in humans.
 
Yoneshiro T(1), Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T,
Saito M.
 
Author information: 
(1)Department of Anatomy, Hokkaido University Graduate School of Medicine,
Sapporo, Japan. yoneshiro@med.hokudai.ac.jp
 
 
Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to 
cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron
emission tomography and computed tomography, we previously reported that BAT
decreases with age and thereby accelerates age-related accumulation of body fat
in humans. Thus, the recruitment of BAT may be effective for body fat reduction. 
In this study, we examined the effects of repeated stimulation by cold and
capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT 
activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure
(EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity
independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 
weeks resulted in a parallel increase in BAT activity and CIT and a concomitant
decrease in body fat mass. Changes in BAT activity and body fat mass were
negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks
increased CIT. These results demonstrate that human BAT can be recruited even in 
individuals with decreased BAT activity, thereby contributing to body fat
reduction.
 
PMCID: PMC3726164
PMID: 23867622
 
-------------
[2] Am J Clin Nutr. 2012 Apr;95(4):845-50. doi: 10.3945/ajcn.111.018606. Epub 2012
Feb 29.
 
Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the
activation of brown adipose tissue in humans.
 
Yoneshiro T(1), Aita S, Kawai Y, Iwanaga T, Saito M.
 
Author information: 
(1)Laboratory of Histology and Cytology, Department of Anatomy, Hokkaido
University Graduate School of Medicine, Sapporo, Japan.
 
BACKGROUND: Capsinoids-nonpungent capsaicin analogs-are known to activate brown
adipose tissue (BAT) thermogenesis and whole-body energy expenditure (EE) in
small rodents. BAT activity can be assessed by [¹⁸F]fluorodeoxyglucose-positron
emission tomography (FDG-PET) in humans.
OBJECTIVES: The aims of the current study were to examine the acute effects of
capsinoid ingestion on EE and to analyze its relation to BAT activity in humans.
DESIGN: Eighteen healthy men aged 20-32 y underwent FDG-PET after 2 h of cold
exposure (19°C) while wearing light clothing. Whole-body EE and skin temperature,
after oral ingestion of capsinoids (9 mg), were measured for 2 h under warm
conditions (27°C) in a single-blind, randomized, placebo-controlled, crossover
design.
RESULTS: When exposed to cold, 10 subjects showed marked FDG uptake into adipose 
tissue of the supraclavicular and paraspinal regions (BAT-positive group),
whereas the remaining 8 subjects (BAT-negative group) showed no detectable
uptake. Under warm conditions (27°C), the mean (±SEM) resting EE was 6114 ± 226
kJ/d in the BAT-positive group and 6307 ± 156 kJ/d in the BAT-negative group
(NS). EE increased by 15.2 ± 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7
± 3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids (P <
0.01). Placebo ingestion produced no significant change in either group. Neither 
capsinoids nor placebo changed the skin temperature in various regions, including
regions close to BAT deposits.
CONCLUSION: Capsinoid ingestion increases EE through the activation of BAT in
humans. This trial was registered at http://www.umin.ac.jp/ctr/as UMIN
000006073.
 
PMID: 22378725
 

There will never be peace in the world while there are animals in our bellies.





Also tagged with one or more of these keywords: Cold Exposure, Exercise, Fasting, UCPs, UCP1, UCP3, FGF21